May I borrow your brains, please? (23andMe results)

Hi all, I've been learning so much by reading all the threads. (thank you!) I am SO impressed by your knowledge. Hopefully, you will be able to share a little with me.

I spent years trying to figure out my Hashimoto's, (hypothyroidism) but it appears as if I have deeper issues for what's been going on. (mainly extreme fatigue & brain fog)

I just received my 23andMe raw data, and plugged it into Genetic Genie. (file attached) I also used livewello.com, but that's 20 pages, so I'll spare you!

Because of the CBS SNP, I've given up anything sulfur related (foods, NAC, Liver Detox, etc) but I just don't know my next steps. Since I do have the MTHFR C677T SNP, I know I need to address that, (amongst many other things - yikes!) so I'm asking for a little guidance.

Thank you in advance for any help!
Wintering

Attached Files:

Have I asked for your assistance incorrectly? If so, please forgive my defective DNA. (my long lost mensa IQ must be snickering) To try and make this short ... *fingers crossed* .... 4 years ago I had a very stressful time. Within weeks, my thyroid crashed, I developed a gluten intolerance, my brain function took a hike, and developed asthma.

All along, I've been focusing on my thyroid. My levels are finally getting happy-ish, but I'm not feeling the improvement. My cousin suggested I try 23andMe for answers. I did .... and (especially with the brain fog) am overwhelmed. If it helps:

I have been all over Dr. Ben & Dr. Amy's sites, livewello, Genetic Gene, NutraHacker, and here! The things that confuse me the most right now are: Should I just start with an L-5-MTHF supplement since I'm so confused about the Methyl B12 - vs - Hydroxy B12 difference? (I've read several battles on this forum) Or, should I try Dr. Amy or Dr. Ben's "all in one" supplement"? My reports say take Methyl B12 for MTRR, but avoid it for COMT. And how concerned should I be about sulfur, since I've been eating a clean / sulfur free diet for months? I finally found a new Functional Doctor who claims to be MTHFR savvy, but he wants to start me on IV Glutathione. (it's sulfur based - not good for CBS, correct?)

If I'm in the wrong area for guidance, please let me know where to turn. Or ...... I guess I'll just tuck my tail snps between my (defective/confused) legs .....

Have I asked for your assistance incorrectly? If so, please forgive my defective DNA. (my long lost mensa IQ must be snickering) To try and make this short ... *fingers crossed* .... 4 years ago I had a very stressful time. Within weeks, my thyroid crashed, I developed a gluten intolerance, my brain function took a hike, and developed asthma.

All along, I've been focusing on my thyroid. My levels are finally getting happy-ish, but I'm not feeling the improvement. My cousin suggested I try 23andMe for answers. I did .... and (especially with the brain fog) am overwhelmed. If it helps:

I have been all over Dr. Ben & Dr. Amy's sites, livewello, Genetic Gene, NutraHacker, and here! The things that confuse me the most right now are: Should I just start with an L-5-MTHF supplement since I'm so confused about the Methyl B12 - vs - Hydroxy B12 difference? (I've read several battles on this forum) Or, should I try Dr. Amy or Dr. Ben's "all in one" supplement"? My reports say take Methyl B12 for MTRR, but avoid it for COMT. And how concerned should I be about sulfur, since I've been eating a clean / sulfur free diet for months? I finally found a new Functional Doctor who claims to be MTHFR savvy, but he wants to start me on IV Glutathione. (it's sulfur based - not good for CBS, correct?)

If I'm in the wrong area for guidance, please let me know where to turn. Or ...... I guess I'll just tuck my tail snps between my (defective/confused) legs .....

I honestly don't know what I've done wrong. But to be completely ignored is shameful. On the forums I host (bereavement) at least someone would acknowledge my existence, and let me know someone would reply soon.

I honestly don't know what I've done wrong. But to be completely ignored is shameful. On the forums I host (bereavement) at least someone would acknowledge my existence, and let me know someone would reply soon.

I wish you all peace and health ....

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Hey, not to fret. I saw your message last week, but have been unable to answer until now. I'm going to send you a document via Conversation, so look for the red flag alert at the top right of the page.

Hi @Wintering. I am just learning about my own 23andme results so I don't know enough to help you myself. There are a few people on PR who are very knowledgable and generous with their help. You need to tag them like this to get their attention. @caledonia @Critterina @Valentijn

@caledonia also has some fabulous information under her signature which you may want to read.

Hope this helps you and you are also able to share with and help others on PR

Hey, not to fret. I saw your message last week, but have been unable to answer until now. I'm going to send you a document via Conversation, so look for the red flag alert at the top right of the page.

Hey, not to fret. I saw your message last week, but have been unable to answer until now. I'm going to send you a document via Conversation, so look for the red flag alert at the top right of the page.

Hi @Wintering. I am just learning about my own 23andme results so I don't know enough to help you myself. There are a few people on PR who are very knowledgable and generous with their help. You need to tag them like this to get their attention. @caledonia @Critterina @Valentijn

@caledonia also has some fabulous information under her signature which you may want to read.

Hope this helps you and you are also able to share with and help others on PR

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Hi AndyPandy, thank you so much for your reply! {{{hugs}}} I scrolled through the forum, but couldn't find a recent post from you. If I knew how to help, I'd definitely try! And Ha, now I need to learn (with my brain fog) how to tag? Yikes! Ahem, for my virgin attempt, does this work? @AndyPandy ??? Maaaan, I miss my brain cells!
Thank you, thank you, thank you for your reply....
Wintering

@Wintering Just a thought, but maybe there are certain SNPs that are associated with Hashimotos? Is there anything on the thyroid forums regarding that? I'm thinking about an enzyme that does something with iodine. I haven't looked into this as I don't have Hashimoto's. It just crossed my mind.

@Wintering yes I got an alert that you had tagged me! You will see that the alerts come up in a red box top right of the screen when you are logged on.

If you want to see what someone has been posting you can get there by clicking on their name under their photo or avatar. Click on Profile Page and it will take you to information about that person. You can also elect to "follow" people.

If you are not sure what to do try the help function at the top of the screen.

Sorry, @Wintering , for nobody responding sooner. I see that Caledonia is sending you something, and she's good. I'll share my thoughts, too. Of course you know what they say: a man with one watch knows what time it is; a man with two watches is never sure. You know that there are a lot of opinions that the experts have. Well, it's the same with us non-experts. You'll need to consider them and make up your own mind what you're going to do.

My opinion is that the CBS that you are +/- for, is not a very strong mutation. Yes, it does mildly accelerate the sulfur exiting the methyl cycle, but in and of itself, I'm not convinced that it causes sulfur problems. Do you have exacerbated symptoms from eggs or onions? Or other sulfur-containing foods? Did the low sulfur diet noticeably help you? I do believe that some people have sulfur problems, not just everybody who has a CBS mutation. So, you can probably answer for yourself whether you need to continue to low sulfur diet. (Now, sulfites may be a separate situation - you can be sensitive to them without having other sulfur issues. You can Google "naming the demons" for an exhaustive discussion of one person's sulfite sensitivities.)

Yes, if I were you, I would start with methylfolate. Start with as low a dose as you feel you need to. Some people grind up a tablet and just put a few sprinkles on their tongue and watch for any negative symptoms. I personally started at 1 mg, which is what I use now, but it was recommended by a healthcare practitioner. But I have different SNPs than you, and you may end up needing more, or maybe less, at least for a while. Solgar is the brand I use, and it's generally regarded as good in the discussion on this forum.

I think I would also, if I were you, use one form of B12. Because you do have the COMT and MAO A homozygous, maybe use the hydroxB12. Your need for methylB12, based on your SNPs isn't all that strong, and I don't know if you have any signs of B12 deficiency (like peripheral neuropathy). So, I think hydroxy is a fine place to start. If you get daring after a while and are willing to risk $7 and possible "overmethylation", switch out your hydroxy for an equivalent dose of methylB12, just once, and see how you do with the Enzymatic Therapies brand.

Personally, I think that the SNPs are good enough evidence to use those two supplements. I'd really like to have an understanding of symptoms and lab results before considering other supplements to use. For example, you have two vitamin D receptor heterozygous SNPs. Depending on where your Vitamin D levels are, you and your healthcare practitioner may want to add vitamin D. The other things I'd wonder about is your homocysteine level, which may be elevated due to your MTHFR C677T and your BHMT-08, even though the first is heterozygous. In fact, that would be the first thing I would want a lab result for. If it's high, the folate and B12 may take it down enough. If they don't, then you might consider TMG (trimethyl glycine). But it might be too much in terms of extra methyl groups for you with the COMT and MAO A SNPs. I'd really want to have some idea that you need it before risking it.

So those are my thoughts. I'm not a medical person or any kind of expert. I've looked at the cycles and how they interact, but there is still a lot I don't understand. Please consider input from a lot of sources and decide for yourself which ideas seem to resonate with you and what you're going to try.

I honestly don't know what I've done wrong. But to be completely ignored is shameful. On the forums I host (bereavement) at least someone would acknowledge my existence, and let me know someone would reply soon.

I wish you all peace and health ....

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Don't take it personally Wintering. People aren't ignoring you. You're in a forum of sick people with little energy and many cognitive deficits. Some days that I have enough energy to be on here at all I'm only up to reading one or two posts, and not up to formulating any responses that take thinking effort. I know there are many here like me.

If your thread is being overlooked add another post which will bump it to the top of the list again and folks will comment when they're up to it.

You'll notice from my signature I'm homozygous for both COMT snps. I have no problem with taking Methyl B12. A trial of Methyl B12 will tell you whether or not you can tolerate it. I don't believe it is something that will harm you if you can't tolerate it. It might just lead to some unpleasant symptoms for a short time. A trial of Hydroxy B12 would show you whether you can convert it efficiently or not. If you feel nothing from it, you're probably not utilising it.

@Wintering Just a thought, but maybe there are certain SNPs that are associated with Hashimotos? Is there anything on the thyroid forums regarding that? I'm thinking about an enzyme that does something with iodine. I haven't looked into this as I don't have Hashimoto's. It just crossed my mind.

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If you run your SNPs through the MTHFRsupport.com report, it has a section for thyroid related SNPs. That's a paid report, I think about $20. I don't really know what that knowledge does for you, however.

@Wintering Just a thought, but maybe there are certain SNPs that are associated with Hashimotos? Is there anything on the thyroid forums regarding that? I'm thinking about an enzyme that does something with iodine. I haven't looked into this as I don't have Hashimoto's. It just crossed my mind.

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Hi @Aileen, thank you so much for your reply. Since I'm reading everything I can get my hands on, I haven't had the chance to "play" with my livewello sandbox just yet, but I'm certain there must be a thyroid snp in there somewhere! (My Mother also has Hashimotos) The thyroid gland is basically the canary in the coal mine. (once it crashes ... other "things" are soon to follow!)
Thanks again for thinking of me! {{{hugs}}}

Sorry, @Wintering , for nobody responding sooner. I see that Caledonia is sending you something, and she's good. I'll share my thoughts, too. Of course you know what they say: a man with one watch knows what time it is; a man with two watches is never sure. You know that there are a lot of opinions that the experts have. Well, it's the same with us non-experts. You'll need to consider them and make up your own mind what you're going to do.

Click to expand...

Thank you, and *giggles* .... I think all my watches are broken, so I'll gladly take a peak at yours!

My opinion is that the CBS that you are +/- for, is not a very strong mutation. Yes, it does mildly accelerate the sulfur exiting the methyl cycle, but in and of itself, I'm not convinced that it causes sulfur problems. Do you have exacerbated symptoms from eggs or onions? Or other sulfur-containing foods? Did the low sulfur diet noticeably help you? I do believe that some people have sulfur problems, not just everybody who has a CBS mutation. So, you can probably answer for yourself whether you need to continue to low sulfur diet. (Now, sulfites may be a separate situation - you can be sensitive to them without having other sulfur issues. You can Google "naming the demons" for an exhaustive discussion of one person's sulfite sensitivities.)

Click to expand...

Hmmmmm, great questions! Once I eliminated anything sulfur related, (about 2 weeks ago) I really didn't notice a difference. (Still feel like warmed over puppy poo) I only have a reaction to eggs if I have them a few times a week, (TMI alert ... gassy, sorry!) and raw onions yes, but cooked, no reactio. I've been reading on Dr. Ben's site that we need to fix any CBS mutation before addressing MTHFR. (???)

Yes, if I were you, I would start with methylfolate. Start with as low a dose as you feel you need to. Some people grind up a tablet and just put a few sprinkles on their tongue and watch for any negative symptoms. I personally started at 1 mg, which is what I use now, but it was recommended by a healthcare practitioner. But I have different SNPs than you, and you may end up needing more, or maybe less, at least for a while. Solgar is the brand I use, and it's generally regarded as good in the discussion on this forum.

I think I would also, if I were you, use one form of B12. Because you do have the COMT and MAO A homozygous, maybe use the hydroxB12. Your need for methylB12, based on your SNPs isn't all that strong, and I don't know if you have any signs of B12 deficiency (like peripheral neuropathy). So, I think hydroxy is a fine place to start. If you get daring after a while and are willing to risk $7 and possible "overmethylation", switch out your hydroxy for an equivalent dose of methylB12, just once, and see how you do with the Enzymatic Therapies brand.

Personally, I think that the SNPs are good enough evidence to use those two supplements. I'd really like to have an understanding of symptoms and lab results before considering other supplements to use. For example, you have two vitamin D receptor heterozygous SNPs. Depending on where your Vitamin D levels are, you and
your healthcare practitioner may want to add vitamin D. The other things I'd wonder about is your homocysteine level, which may be elevated due to your MTHFR C677T and your BHMT-08, even though the first is heterozygous. In fact, that would be the first thing I would want a lab result for. If it's high, the folate and B12 may take it down enough. If they don't, then you might consider TMG (trimethyl glycine). But it might be too much in terms of extra methyl groups for you with the COMT and MAO A SNPs. I'd really want to have some idea that you need it before risking it.

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Because of my thyroid, I'm already supplementing with 5000 iu D3. (lab values were good) The doctor also checked my B12, and it was (surprisingly?) within range. But, the one big red flag was my Homocysteine level - very high at 22.2. (I guess I'm a heart attack on a plate, eh?)

So those are my thoughts. I'm not a medical person or any kind of expert. I've looked at the cycles and how they interact, but there is still a lot I don't understand. Please consider input from a lot of sources and decide for yourself which ideas seem to resonate with you and what you're going to try.

Don't take it personally Wintering. People aren't ignoring you. You're in a forum of sick people with little energy and many cognitive deficits. Some days that I have enough energy to be on here at all I'm only up to reading one or two posts, and not up to formulating any responses that take thinking effort. I know there are many here like me.

If your thread is being overlooked add another post which will bump it to the top of the list again and folks will comment when they're up to it.

You'll notice from my signature I'm homozygous for both COMT snps. I have no problem with taking Methyl B12. A trial of Methyl B12 will tell you whether or not you can tolerate it. I don't believe it is something that will harm you if you can't tolerate it. It might just lead to some unpleasant symptoms for a short time. A trial of Hydroxy B12 would show you whether you can convert it efficiently or not. If you feel nothing from it, you're probably not utilising it.

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Thank you so much @Sea! And boy, I can surely relate! I guess bumping it up for the 3rd time was the charm.

Once I eliminated anything sulfur related, (about 2 weeks ago) I really didn't notice a difference. (Still feel like warmed over puppy poo) I only have a reaction to eggs if I have them a few times a week, (TMI alert ... gassy, sorry!) and raw onions yes, but cooked, no reactio. I've been reading on Dr. Ben's site that we need to fix any CBS mutation before addressing MTHFR. (???)

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So...I'm going out on a limb here and saying that the "really didn't notice a difference" is probably your biggest indicator. There has been some misinformation going around about CBS being a huge deal. Someone read a report (the research was valid) and mistook the findings for something artificially created in the laboratory (a CBS enzyme with a big chunk cut off) for what happens with the CBS C699T mutation (a single nucleotide swapped out). It appears that one person misread the report and a lot of people repeated it. I stopped reading Dr. Ben when I found I had the MTHFR A1298C SNP and his site only addressed the 677T mutation; I think he has made updates to his site. I don't know what is there now, or if he has made what I feel is too big a deal out of CBS or not.

Of course, there are two sides to every coin, and I would be wrong to say that nobody with CBS has sulfur problems. I think some people have sulfur problems, really and truly. I just don't think it's CBS alone that causes them. Maybe it's SUOX, maybe something else. I like experiential data. I like hard data better, but I don't discount your impressions at all.

NutraHacker is really good at that. I have several conflicting suggestions based on my SNPs from NutraHacker. Note that they don't publish their references for their suggestions. Take that report with a grain of salt.

Yes, it's OK to post links. And actually, I don't think that is a bad product. Personally, I can't use the pyridoxine in the form it has; I need pyridoxine-5-phosphate. If you were just going to buy one thing (I can't see the price without logging in), that would be a good place to start. You hit the crucial difference, though: you can't take baby steps, and you can't alter one thing without altering the other things in it proportionally. Obviously, you understand.

Because of my thyroid, I'm already supplementing with 5000 iu D3. (lab values were good) The doctor also checked my B12, and it was (surprisingly?) within range. But, the one big red flag was my Homocysteine level - very high at 22.2. (I guess I'm a heart attack on a plate, eh?)

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OK about the Vitamin D. Do you get enough green leafies? Without enough Vitamin K, Vitamin D can end up placing the calcium in the blood instead of the bones. Not a good thing, particularly with high homocysteine.

B12 in serum, if I understand correctly, measures both active and inactive. Your MTRR A66G +/- means that half your enzyme for methylating (activating) B12 don't work so well. So normal serum levels mean that your intake is enough, but not necessarily that your functionality is enough. If you increase the available B12 using hydroxy form, you'll still have less than efficient conversion, but as more is available, more will be converted. If you use methylB12, you skip the inefficient enzyme.

High homocysteine...actually that's not a surprise. There are three ways that homocysteine gets used up. One uses methylfolate (which you have less of through the MTHFR C667T +/-) and methylB12 (which you have less of through the MTRR A66G +/-). The second way is through the BHMT pathway (and yours is significantly slowed with the BHMT 08 being +/+. At first I wrote 'blocked' but that's probably too strong. I don't know what % efficiency it actually works at). Supplementing Betaine (Trimethyl Glycine, TMG) helps accelerate that pathway. The third way - get this - is through the CBS pathway - which in you is ACCELERATED by your C669T +/- SNP. Is your CBS giving you problems? Apparently not enough to lower your homocysteine!

Some of the things that can slow down the accelerated CBS pathway are lack of active B6 (the pyridoxine-5-phosphate) and lack of magnesium. There are also toxic blockers, like perhaps mercury or arsenic, but I don't know much about them. Let's concentrate on the factors you can add if you need to. The link to what your doctor wants you to take has the B6, albeit in a form that needs activation. Did they test your magnesium (Mg) level?

So, in the end, the product you linked to has methylfolate, methylB12, B6, and TMG. All good puts, as far as I can see. It has riboflavin, too, that I haven't identified a need for in your SNPs. But we didn't identify the need in mine, either, and when I did the NutraEval, riboflavin was my biggest need. So I'm not going to say it's bad for you. Two questions to consider: (1) Cost of the recommended product vs. cost of the individual products, and (2) What does it do to your relationship with this healthcare practitioner if you use what he recommended vs. buying the products independently?

Your practitioner seems to have made a good recommendation (said like I know what I'm talking about! ). I would recommend additionally that you check your magnesium on your lab results and ask him whether or not to supplement with that, too. I like him and am glad you're working with him. There's another forum on doctors here. I don't have CFS/ME so I don't read it. But if he turns out to be a good guy, think of making a post there so others can find him

Critterina
P.S. I think I'm the only person I know who knows they can't activate pyridoxine hydrochloride. It may be fairly rare, and I don't know what gene is responsible or whether I have SNPs in it.

So...I'm going out on a limb here and saying that the "really didn't notice a difference" is probably your biggest indicator. There has been some misinformation going around about CBS being a huge deal. Someone read a report (the research was valid) and mistook the findings for something artificially created in the laboratory (a CBS enzyme with a big chunk cut off) for what happens with the CBS C699T mutation (a single nucleotide swapped out). It appears that one person misread the report and a lot of people repeated it. I stopped reading Dr. Ben when I found I had the MTHFR A1298C SNP and his site only addressed the 677T mutation; I think he has made updates to his site. I don't know what is there now, or if he has made what I feel is too big a deal out of CBS or not.
......
OK about the Vitamin D. Do you get enough green leafies? Without enough Vitamin K, Vitamin D can end up placing the calcium in the blood instead of the bones. Not a good thing, particularly with high homocysteine.

B12 in serum, if I understand correctly, measures both active and inactive. Your MTRR A66G +/- means that half your enzyme for methylating (activating) B12 don't work so well. So normal serum levels mean that your intake is enough, but not necessarily that your functionality is enough. If you increase the available B12 using hydroxy form, you'll still have less than efficient conversion, but as more is available, more will be converted. If you use methylB12, you skip the inefficient enzyme.

High homocysteine...actually that's not a surprise. There are three ways that homocysteine gets used up. One uses methylfolate (which you have less of through the MTHFR C667T +/-) and methylB12 (which you have less of through the MTRR A66G +/-). The second way is through the BHMT pathway (and yours is significantly slowed with the BHMT 08 being +/+. At first I wrote 'blocked' but that's probably too strong. I don't know what % efficiency it actually works at). Supplementing Betaine (Trimethyl Glycine, TMG) helps accelerate that pathway. The third way - get this - is through the CBS pathway - which in you is ACCELERATED by your C669T +/- SNP. Is your CBS giving you problems? Apparently not enough to lower your homocysteine!

Some of the things that can slow down the accelerated CBS pathway are lack of active B6 (the pyridoxine-5-phosphate) and lack of magnesium. There are also toxic blockers, like perhaps mercury or arsenic, but I don't know much about them. Let's concentrate on the factors you can add if you need to. The link to what your doctor wants you to take has the B6, albeit in a form that needs activation. Did they test your magnesium (Mg) level?

So, in the end, the product you linked to has methylfolate, methylB12, B6, and TMG. All good puts, as far as I can see. It has riboflavin, too, that I haven't identified a need for in your SNPs. But we didn't identify the need in mine, either, and when I did the NutraEval, riboflavin was my biggest need. So I'm not going to say it's bad for you. Two questions to consider: (1) Cost of the recommended product vs. cost of the individual products, and (2) What does it do to your relationship with this healthcare practitioner if you use what he recommended vs. buying the products independently?

Your practitioner seems to have made a good recommendation (said like I know what I'm talking about! ). I would recommend additionally that you check your magnesium on your lab results and ask him whether or not to supplement with that, too. I like him and am glad you're working with him. There's another forum on doctors here. I don't have CFS/ME so I don't read it. But if he turns out to be a good guy, think of making a post there so others can find him

Critterina
P.S. I think I'm the only person I know who knows they can't activate pyridoxine hydrochloride. It may be fairly rare, and I don't know what gene is responsible or whether I have SNPs in it.

So, you think I'd actually be able to "feel" a difference after being off eggs, onions, sup's, etc. for a few weeks? I admit, I'm relieved to learn the my CBS isn't that bad, but after reading the heartfixer methylation site, me'eyes were spinning!

Hmmmm, green leafies, eh? Not as much as I should because of my thyroid / goitrogenic and hemochromatosis / iron. It looks like I better look into Vitamin K.

Very interesting about your call on magnesium. It was below the lab's ranges too. (even though I supplement with 500mg Magnesium Citrate) The only other two things that are whackadoodle were high DHEA and high Testosterone. (the last time I looked, I'm still a girl!) My new doc did check, and I'm not pre-diabetic. (at least something positive!) I'm not to sure about heavy metals. I don't have any mercury fillings, but I do have titanium dental implants.

NutraEval, eh? I did a quick search, and that looks very interesting. I'll have to ask the new doc when I see him later in the week. And if he's lives up to my first impression, I'll be sure mention him on the other forum.

Oh Critterina, I know this is a silly question, but with all your knowledge, may I ask if you're feeling tip-top now? I've got my fingers (eyes, toes, legs) crossed that once I get this figured out, I'll be able to have a life again. I'm so glad you've figured out how to heal yourself, and you're sharing your knowledge with me. ♥

Sorry to say, your doc is not knowledgeable. This supplement (unless taken with at least 2000mcg or larger of sublingual B12) would be guaranteed to cause methyl trapping in the primary methylation cycle.

Not only does the supplement have more methylfolate than B12, the B12 contained in it is oral, which only absorbs 1-2%. So basically, it's like taking 2000mcg of methylfolate without any B12 - bad idea.

The betaine (TMG) would support the secondary methylation cycle. So perhaps that's why people think this vitamin might be working.

Plus the starting amounts are way too much for ME patients, who are typically very debilitated. Start Low and Go Slow or pay the consequences...

Sorry to say, your doc is not knowledgeable. This supplement (unless taken with at least 2000mcg or larger of sublingual B12) would be guaranteed to cause methyl trapping in the primary methylation cycle.

Not only does the supplement have more methylfolate than B12, the B12 contained in it is oral, which only absorbs 1-2%. So basically, it's like taking 2000mcg of methylfolate without any B12 - bad idea.

The betaine (TMG) would support the secondary methylation cycle. So perhaps that's why people think this vitamin might be working.

Plus the starting amounts are way too much for ME patients, who are typically very debilitated. Start Low and Go Slow or pay the consequences...

Confused, who me? Does this mean that you'd suggest I address my BHMT, CBS, and AHCY levels first?
If you have an idea of where I should begin, please let me know.
I know to go slow or pay the consequences ....... but where to begin?